The quality of life in patients carrying implantable cardioverter-defibrillators (ICDs) is affected by the occurrence of defibrillation shocks. Consequently, significant efforts have been made to decrease the shock energy for less pain and battery drain. A major progress came in the 80s when biphasic shocks were found to be far more efficient than monophasic shocks in defibrillation. Subsequent efforts in optimizing shock waveforms have produced only marginal improvement, suggesting a conceptual breakthrough is required to prompt more significant advances. Recently, a new opportunity in developing novel defibrillation methods has emerged due to 1) the realization of wavefront organization during fibrillation, and 2) the growing popularity of clinical biventricular pacing/defibrillation devices that allow extra leads to be placed in the ventricles. These new developments hint the potential approach to terminate arrhythmias by detecting wavefront organization in real-time and delivering low-energy pulses on a cycle-to-cycle basis in a spatially distributed manner. This competing renewal proposes a novel approach that uses multi-electrode, synchronized pacing techniques to enforce wavefront organization and terminate fibrillation with an energy requirement at least two orders of magnitude lower than the strong shock approach. An interactive, imaging-assisted pacing and defibrillation system will be used to detect and pace in the excitable gaps to synchronize wavefronts. Wavefront organization will be evaluated by the occurrence of phase singularities dudng fibrillation. The specific aims are 1) To study the mechanisms of feedback pacing in wavefront synchronization; 2) To evaluate the efficacy of synchronized pacing in terminating fibrillation; 3) To design new defibrillation strategies combining synchronized pacing and high-voltage shocks. Aim 1 will provide mechanistic foundation for optimizing electrode location and spacing in synchronized pacing. Extensive mathematical modeling using cardiac bidomain will be performed in parallel to animal studies to theorize optimal electrode configurations. Aim 2 will establish the role of synchronized pacing as an exclusive means of terminating fibrillation. Aim 3 will test the efficacy of three new defibrillation strategies using pre-shock or post-shock synchronized pacing in addition to the strong shocks. We will use isolated rabbit heart and isolated swine right ventricle in these studies. Successful execution of this project will suggest a novel, low-energy electrical pacing strategy for the management of arrhythmias.